Enhancing future liver remnant hypertrophy: innovative preoperative strategies and emerging technologies

Major hepatectomy remains the only curative option for many primary and secondary liver malignancies, yet postoperative liver failure continues to limit resectability when the future liver remnant (FLR) is insufficient. Over recent decades, a spectrum of strategies has been developed to safely enlarge and optimize FLR volume and function. This review summarizes established and emerging approaches aimed at enhancing preoperative FLR hypertrophy. Conventional methods such as portal vein embolization (PVE) and portal vein ligation (PVL) remain first-line techniques, while associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) achieves rapid but riskier hypertrophy. Liver venous deprivation (LVD) and combined strategies-including transarterial chemoembolization (TACE) plus PVE or radioembolization-offer faster or dual oncologic-regenerative benefits with improved safety profiles. Innovative developments such as pharmacologic modulation [farnesoid X receptor (FXR), FGF19, THR-β, and GLP-1 agonists], growth factor delivery, and stem-cell-based therapies are emerging to enhance both volumetric and functional regeneration, particularly in steatotic or fibrotic livers. Advanced imaging and predictive technologies-such as ^99mTc-mebrofenin hepatobiliary scintigraphy (HBS), four-dimensional (4D)-flow magnetic resonance imaging (MRI), and computed tomography (CT)-based radiomics-enable integrated volumetric-functional assessment and individualized surgical timing. Although PVE remains the benchmark, multimodal, patient-tailored strategies combining hemodynamic, pharmacologic, and cellular interventions, guided by functional imaging, are reshaping the landscape of hepatic surgery. Future randomized trials and translational studies are essential to define optimal algorithms, validate novel therapies, and safely extend curative resection to a broader population of patients with complex liver disease.